Counterions, Polarization and Pore Hydration Relay Drive Ion Permeation through Hydrophobic Pore Formed by the MERS Coronavirus E Protein
- 1Boston University
Abstract
Hydrophobic pores are generally expected to exclude ions because the large desolvation penalty associated with ion transfer cannot be compensated within a nonpolar environment. The envelope (E) protein of Middle East Respiratory Syndrome coronavirus (MERS-CoV) presents a striking exception, conducting cations with high efficiency despite forming a predominantly hydrophobic pore. To resolve this apparent paradox, we combine finite-temperature string simulations with additive and polarizable force fields to determine the minimum free-energy pathways for ion permeation through the MERS E channel. The simulations reveal a cooperative permeation mechanism in which transient counterion association, localized pore hydration, and electronic polarization jointly reduce the desolvation penalty. Rather than acting as passive spectators, counterions transiently chaperone the permeating cation before dissociating within the channel, thereby lowering the energetic cost of charge desolvation while preserving net ionic conductance. Explicit electronic polarization further reshapes the pore hydration landscape and cation-{pi} interactions, leading to substantially reduced free-energy barriers and a permeation mechanism in substantially better agreement with experiment. These results suggest that efficient ion transport through hydrophobic pores arises from the cooperative interplay between electrostatics, polarization and hydration rather than complete pore wetting, providing both a mechanistic framework for MERS E protein function and a general physical principle for ion transport through biological and synthetic hydrophobic nanopores.
Related
- Computational assay of hERG ion permeation and its modulation by small-molecule compounds
- How a polymer filling enhances the rate and selectivity of colloid permeation across mesopores
- MechGate: combining mechanism-derived measures of permeation and efflux to screen small molecule drugs targeting Escherichia coli
- Free-Energy and Position-Dependent Diffusion Profiles Shape Passive Permeation of a Semisynthetic Naphthoquinone across a Model Lipid Bilayer.
- IFN-dependent Gsdmd priming induces pyroptosis in coronavirus-infected healthy cells
BibTeX
@misc{wan2026counterions,
title = {{Counterions, Polarization and Pore Hydration Relay Drive Ion Permeation through Hydrophobic Pore Formed by the MERS Coronavirus E Protein}},
author = {Z. Wan and M. Hong and Q. Cui},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749198},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749198v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Counterions, Polarization and Pore Hydration Relay Drive Ion Permeation through Hydrophobic Pore Formed by the MERS Coronavirus E Protein
AU - Z. Wan
AU - M. Hong
AU - Q. Cui
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749198
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749198v1
AB - Hydrophobic pores are generally expected to exclude ions because the large desolvation penalty associated with ion transfer cannot be compensated within a nonpolar environment. The envelope (E) protein of Middle East Respiratory Syndrome coronavirus (MERS-CoV) presents a striking exception, conducting cations with high efficiency despite forming a predominantly hydrophobic pore. To resolve this apparent paradox, we combine finite-temperature string simulations with additive and polarizable force fields to determine the minimum free-energy pathways for ion permeation through the MERS E channel. The simulations reveal a cooperative permeation mechanism in which transient counterion association, localized pore hydration, and electronic polarization jointly reduce the desolvation penalty. Rather than acting as passive spectators, counterions transiently chaperone the permeating cation before dissociating within the channel, thereby lowering the energetic cost of charge desolvation while preserving net ionic conductance. Explicit electronic polarization further reshapes the pore hydration landscape and cation-{pi} interactions, leading to substantially reduced free-energy barriers and a permeation mechanism in substantially better agreement with experiment. These results suggest that efficient ion transport through hydrophobic pores arises from the cooperative interplay between electrostatics, polarization and hydration rather than complete pore wetting, providing both a mechanistic framework for MERS E protein function and a general physical principle for ion transport through biological and synthetic hydrophobic nanopores.
ER -